A proteomic profile of postpartum cervical repair in mice

A timely and complete uterine cervical tissue repair postpartum is of necessity to prevent obstetrical complications, such as cervicitis, ectropion, hemorrhage, repeated miscarriages or abortions and possibly preterm labor and malignancies. We recently characterized the morphological alterations, as well as changes in angiogenic expression profile in a mice uterine cervix during the immediate postpartum period. Here, we build on this previous study using a proteomic analysis to profile postpartum tissue changes in mice cervix during the same period, the first 48 h of postpartum. The current proteomics data reveal a variable expression of several intermediate filaments, cytoskeletal modulators and proteins with immune and/or wound-healing properties. We conclude that postpartum cervical repair involves a rapid and tightly regulated balance between a host of biological factors, notably between anti- and pro-inflammatory factors, executed by the M1 and M2 macrophage cells, as revealed by proteomics and verified by confocal immunofluorescence. Future studies will assess the suitability of some of the key proteins identified in this study as potential markers for determining the phase of postpartum cervical repair in obstetrical complications, such as cervical lacerations.

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Analysis of the Influence of Jaw Periosteal Cells on Macrophages Phenotype Using an Innovative Horizontal Coculture System

Biomedicines ◽

10.3390/biomedicines9121753 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1753

Author(s):

Fang He ◽

Felix Umrath ◽

Christiane von Ohle ◽

Siegmar Reinert ◽

Dorothea Alexander

Keyword(s):

Macrophage Polarization ◽

Maxillofacial Surgery ◽

Inflammatory Factors ◽

Osteogenic Potential ◽

Oral And Maxillofacial Surgery ◽

M2 Macrophage ◽

Macrophage Phenotype ◽

Flow Cytometric ◽

Coculture System ◽

Gene And Protein Expression

Jaw periosteum-derived mesenchymal stem cells (JPCs) represent a promising cell source for bone tissue engineering in oral and maxillofacial surgery due to their high osteogenic potential and good accessibility. Our previous work demonstrated that JPCs are able to regulate THP-1-derived macrophage polarization in a direct coculture model. In the present study, we used an innovative horizontal coculture system in order to understand the underlying paracrine effects of JPCs on macrophage phenotype polarization. Therefore, JPCs and THP-1-derived M1/M2 macrophages were cocultured in parallel chambers under the same conditions. After five days of horizontal coculture, flow cytometric, gene and protein expression analyses revealed inhibitory effects on costimulatory and proinflammatory molecules/factors as well as activating effects on anti-inflammatory factors in M1 macrophages, originating from multiple cytokines/chemokines released by untreated and osteogenically induced JPCs. A flow cytometric assessment of DNA synthesis reflected significantly decreased numbers of proliferating M1/M2 cells when cocultured with JPCs. In this study, we demonstrated that untreated and osteogenically induced JPCs are able to switch macrophage polarization from a classical M1 to an alternative M2-specific phenotype by paracrine secretion, and by inhibition of THP-1-derived M1/M2 macrophage proliferation.

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Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.639476 ◽

2022 ◽

Vol 8 ◽

Author(s):

Zhi Li ◽

Miao Nie ◽

Liming Yu ◽

Dengshun Tao ◽

Qiang Wang ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Notch Signaling ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Macrophage Polarization ◽

Notch Signaling Pathway ◽

Inflammatory Factors ◽

M2 Macrophage ◽

M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

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Macrophage Populations and Expression of Regulatory Inflammatory Factors in Hepatic Macrophage-depleted Rat Livers under Lipopolysaccharide (LPS) Treatment

Toxicologic Pathology ◽

10.1177/0192623318776898 ◽

2018 ◽

Vol 46 (5) ◽

pp. 540-552 ◽

Cited By ~ 5

Author(s):

Munmun Pervin ◽

Mohammad Rabiul Karim ◽

Mizuki Kuramochi ◽

Takeshi Izawa ◽

Mitsuru Kuwamura ◽

...

Keyword(s):

Low Dose ◽

Inflammatory Factors ◽

M2 Macrophage ◽

Related Factors ◽

Macrophage Activity ◽

Hepatic Macrophages ◽

Tnf Α ◽

Macrophage Populations ◽

Rat Livers ◽

Lps Treatment

To investigate the significance of the appearance of hepatic macrophages and expression of inflammatory factors in normal and macrophage-depleted livers, hepatic macrophages were depleted with liposome (Lipo)-encapsulated clodronate (CLD; 50 mg/kg, i.v.) followed by lipopolysaccharide (LPS) administration (0.1 mg/kg, i.p.) in F344 rats (CLD + LPS). Vehicle control rats (Lipo + LPS) received empty-Lipo before LPS. The low dose of LPS did not result in microscopic changes in the liver in either treatment group but did modulate M1 and M2 macrophage activity in Lipo + LPS rats without altering repopulating hepatic macrophages in CLD + LPS rats. LPS treatment in Lipo + LPS rats dramatically increased the M1 (IL-1β, IL-6, TNF-α, and MCP-1) but not M2 macrophage-related factors (IL-4 and CSF-1) compared to CLD + LPS rats. In the CLD + LPS rats, the M2 macrophage-related factors IL-4 and CSF-1 were elevated. In conclusion, low-dose LPS activated hepatic macrophages in rat livers without causing liver injury or stimulating repopulating hepatic macrophages. These data suggest that LPS may alter the liver microenvironment by modulating M1 or M2 macrophage-related inflammatory mediators and macrophage-based hepatotoxicity.

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Inflammation in Complicated Pregnancy and Its Outcome

American Journal of Perinatology ◽

10.1055/s-0036-1582397 ◽

2016 ◽

Vol 33 (14) ◽

pp. 1337-1356 ◽

Cited By ~ 60

Author(s):

Ram Kalagiri ◽

Timothy Carder ◽

Saiara Choudhury ◽

Niraj Vora ◽

Amie Ballard ◽

...

Keyword(s):

Preterm Labor ◽

Maternal Obesity ◽

Normal Pregnancy ◽

Adverse Outcomes ◽

Therapeutic Interventions ◽

Inflammatory Factors ◽

Diagnostic Tools ◽

Inflammatory Reactions ◽

Mortality And Morbidity

Background Normal pregnancy relies on a careful balance between immune tolerance and suppression. It is known that strict regulation of maternal immune function, in addition to components of inflammation, is paramount to successful pregnancy, and any imbalance between proinflammatory and anti-inflammatory cytokines and chemokines can lead to aberrant inflammation, often seen in complicated pregnancies. Inflammation in complicated pregnancies is directly associated with increased mortality and morbidity of the mother and offspring. Aberrant inflammatory reactions in complicated pregnancies often lead to adverse outcomes, such as spontaneous abortion, preterm labor, intrauterine growth restriction, and fetal demise. The role of inflammation in different stages of normal pregnancy is reviewed, compared, and contrasted with aberrant inflammation in complicated pregnancies. The complications addressed are preterm labor, pregnancy loss, infection, preeclampsia, maternal obesity, gestational diabetes mellitus, autoimmune diseases, and inflammatory bowel disease. Aim This article examines the role of various inflammatory factors contributing to aberrant inflammation in complicated pregnancies. By understanding the aberrant inflammatory process in complicated pregnancies, novel diagnostic tools and therapeutic interventions for modulating it appropriately can be identified.

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Pathophysiology of Acute Kidney Injury, Repair, and Regeneration

10.1093/med/9780199653461.003.0030 ◽

2014 ◽

Author(s):

Ching-Wei Tsai ◽

Sanjeev Noel ◽

Hamid Rabb

Keyword(s):

Acute Kidney Injury ◽

Kidney Disease ◽

Critical Role ◽

Recovery Period ◽

Kidney Tissue ◽

Kidney Injury ◽

Inflammatory Factors ◽

Phase Cell ◽

M2 Macrophage ◽

Renal Stem Cells

Acute kidney injury (AKI), regardless of its aetiology, can elicit persistent or permanent kidney tissue changes that are associated with progression to end-stage renal disease and a greater risk of chronic kidney disease (CKD). In other cases, AKI may result in complete repair and restoration of normal kidney function. The pathophysiological mechanisms of renal injury and repair include vascular, tubular, and inflammatory factors. The initial injury phase is characterized by rarefaction of peritubular vessels and engagement of the immune response via Toll-like receptor binding, activation of macrophages, dendritic cells, natural killer cells, and T and B lymphocytes. During the recovery phase, cell adhesion molecules as well as cytokines and chemokines may be instrumental by directing the migration, differentiation, and proliferation of renal epithelial cells; recent data also suggest a critical role of M2 macrophage and regulatory T cell in the recovery period. Other processes contributing to renal regeneration include renal stem cells and the expression of growth hormones and trophic factors. Subtle deviations in the normal repair process can lead to maladaptive fibrotic kidney disease. Further elucidation of these mechanisms will help discover new therapeutic interventions aimed at limiting the extent of AKI and halting its progression to CKD or ESRD.

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CXCL16/CXCR6 Axis in Adipocytes Differentiated from Human Adipose Derived Mesenchymal Stem Cells Regulates Macrophage Polarization

Cells ◽

10.3390/cells10123410 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3410

Author(s):

Seung-Cheol Lee ◽

Yoo-Jung Lee ◽

Inho Choi ◽

Min Kim ◽

Jung-Suk Sung

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Macrophage Polarization ◽

Inflammatory Factors ◽

M2 Macrophage ◽

M2 Polarization ◽

Chemokine Ligand ◽

Anti Inflammatory ◽

Underlying Mechanisms

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.

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Some Molecular Mechanisms of Cervical Ripening

International Journal of Biomedicine ◽

10.21103/article10(4)_ra3 ◽

2020 ◽

Vol 10 (4) ◽

pp. 324-329

Author(s):

Yu. Grigorieva ◽

G. Suvorova ◽

A. Chaulin ◽

S. Yukhimets ◽

S. Chemidronov ◽

...

Keyword(s):

Extracellular Matrix ◽

Preterm Labor ◽

Structural Changes ◽

Molecular Mechanisms ◽

Cervical Ripening ◽

Inflammatory Factors ◽

Cervical Insufficiency ◽

Cervical Remodeling ◽

Novel Approaches

Cervical remodeling is an active dynamic process that begins long before the onset of labor. The optimal course of the cervical ripening/remodeling processes is a prerequisite for successful vaginal delivery. Cervical remodeling is a slow progressive process that begins early in mammalian pregnancies, and can be loosely divided into four overlapping phases termed softening, ripening, dilation/labor, and postpartum repair. This review discusses some aspects of structural changes in the cervix at different stages of cervical ripening. In particular, the role of cervical epithelia, immune-inflammatory factors/cells, and components of the cervical extracellular matrix in cervical ripening is considered. A better understanding of the molecular-biochemical and histophysiological processes occurring during cervical remodeling is critical for the development of novel approaches to treat cervical insufficiency, preterm labor, and postpartum cervical disorders associated with its integrity.

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The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications

Mediators of Inflammation ◽

10.1155/2017/8162421 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 56

Author(s):

Anna Alisi ◽

Guido Carpino ◽

Felipe L. Oliveira ◽

Nadia Panera ◽

Valerio Nobili ◽

...

Keyword(s):

Molecular Mechanisms ◽

Macrophage Polarization ◽

Experimental Studies ◽

Inflammatory Factors ◽

M2 Macrophage ◽

Low Grade ◽

Nonalcoholic Fatty Liver ◽

Tissue Macrophage ◽

Phenotype Switch

The obese phenotype is characterized by a state of chronic low-grade systemic inflammation that contributes to the development of comorbidities, including nonalcoholic fatty liver disease (NAFLD). In fact, NAFLD is often associated with adipocyte enlargement and consequent macrophage recruitment and inflammation. Macrophage polarization is often associated with the proinflammatory state in adipose tissue. In particular, an increase of M1 macrophages number or of M1/M2 ratio triggers the production and secretion of various proinflammatory signals (i.e., adipocytokines). Next, these inflammatory factors may reach the liver leading to local M1/M2 macrophage polarization and consequent onset of the histological damage characteristic of NAFLD. Thus, the role of macrophage polarization and inflammatory signals appears to be central for pathogenesis and progression of NAFLD, even if the heterogeneity of macrophages and molecular mechanisms that govern their phenotype switch remain incompletely understood. In this review, we discuss the role of adipose and liver tissue macrophage-mediated inflammation in experimental and human NAFLD. This focus is relevant because it may help researchers that approach clinical and experimental studies on this disease advancing the knowledge of mechanisms that could be targeted in order to revert NAFLD-related fibrosis.

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Exocrine Pancreatic Insufficiency in Diabetes Mellitus: A Complication of Diabetic Neuropathy or a Different Type of Diabetes?

Experimental Diabetes Research ◽

10.1155/2011/761950 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 54

Author(s):

Philip D. Hardt ◽

Nils Ewald

Keyword(s):

Diabetes Mellitus ◽

Diabetic Neuropathy ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Diabetic Patients ◽

Exocrine Insufficiency ◽

Morphological Alterations ◽

Tissue Changes ◽

Pancreatic Exocrine

Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

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Efficacy of pulmonary transplantation of engineered macrophages secreting IL-4 on acute lung injury in C57BL/6J mice

Cell Death and Disease ◽

10.1038/s41419-019-1900-y ◽

2019 ◽

Vol 10 (9) ◽

Author(s):

Huiying Liu ◽

Yuan He ◽

Cheng Lu ◽

Pengfei Zhang ◽

Chenchen Zhou ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Alveolar Macrophages ◽

Tissue Injury ◽

Critical Role ◽

Interleukin 4 ◽

Inflammatory Factors ◽

M2 Macrophage ◽

Th2 Cytokine

Abstract Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of respiratory failure, but currently, no effective pharmacotherapy exists for these disorders. Alveolar macrophages play a critical role in both the acute/initial phase and chronic/resolving phase of ALI, rendering them a potential therapeutic target. Interleukin-4 (IL-4), a Th2 cytokine, not only directly inhibits the secretion of pro-inflammatory factors from macrophages but also drives macrophages to the anti-inflammatory and tissue remodeling M2 type. However, the short half-life of IL-4 in vivo hampers its effect on disease treatment. In this study, macrophages secreting IL-4 (M-IL-4) were established and used to treat ALI through pulmonary macrophage transplantation (PMT). The results showed that highly sustained levels of IL-4 and M2 macrophage markers were detected in mice lungs following pulmonary M-IL-4 transplantation. Furthermore, PMT improved the therapeutic effect by reducing lung inflammation, alleviating tissue injury, reducing alveolar macrophages necrotic cell death, and decreasing mortality in mice with ALI. These results suggest an efficient macrophage-based protein drug delivery strategy, and for the first time, prove the feasibility and efficacy of PMT in ALI treatment.

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